A Single Dose Study In Japanese And Western Healthy Subjects To Investigate The Safety, Tolerability And Pharmacokinetics Of PF-04991532

Sponsor

Pfizer (Industry)

Overall Status

Completed

CT.gov ID

NCT01369277

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

7.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is to investigate the safety, tolerability and pharmacokinetics of single ascending oral doses of PF-04991532 in Japanese healthy subjects. The secondary objective is to investigate the pharmacokinetics and safety of single ascending oral doses of PF-04991532 in Western healthy subjects and to compare the pharmacokinetics between Japanese and Western healthy subjects.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus Diabetes Mellitus, Type 2 Glucose Metabolism Disorders	Drug: PF-04991532 Drug: Placebo Drug: PF-04991532	Phase 1

Detailed Description

Safety/Tolerability and Pharmacokinetics

Study Design

Study Type:

Interventional

Actual Enrollment :

22 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Official Title:

A Phase 1, Randomized, Double Blind, Placebo-Controlled, Single Dose Escalation Study In Japanese Healthy Subjects, And Open Label, Single Dose Study In Western Healthy Subjects To Investigate The Safety, Tolerability, And Pharmacokinetics of PF-04991532.

Study Start Date :

Jun 1, 2011

Actual Primary Completion Date :

Sep 1, 2011

Actual Study Completion Date :

Sep 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Japanese cohort A total of 12 Japanese healthy subjects will be allocated to receive 3 ascending single doses (100 mg, 300 mg and 750 mg) of PF-04991532 or placebo through 3 dosing periods in a randomization ratio of 3:1.	Drug: PF-04991532 Single dose administration of PF-04991532 (100 mg, 300 mg and 750 mg) in tablet formulation under fasted condition. Drug: Placebo Single dose administration of matching placebo in tablet formulation at the fasted state
Experimental: Weterner Cohort 9 western healthy subjects will be enrolled to receive 2 single ascending doses (300 mg and 750 mg) of PF-04991532 through 2 dosing periods.	Drug: PF-04991532 Single dose administration of PF-04991532 (300 mg and 750 mg) in tablet formulation under fasted condition.

Arm

Intervention/Treatment

Experimental: Japanese cohort

A total of 12 Japanese healthy subjects will be allocated to receive 3 ascending single doses (100 mg, 300 mg and 750 mg) of PF-04991532 or placebo through 3 dosing periods in a randomization ratio of 3:1.

Drug: PF-04991532

Single dose administration of PF-04991532 (100 mg, 300 mg and 750 mg) in tablet formulation under fasted condition.

Drug: Placebo

Single dose administration of matching placebo in tablet formulation at the fasted state

Experimental: Weterner Cohort

9 western healthy subjects will be enrolled to receive 2 single ascending doses (300 mg and 750 mg) of PF-04991532 through 2 dosing periods.

Drug: PF-04991532

Single dose administration of PF-04991532 (300 mg and 750 mg) in tablet formulation under fasted condition.

Outcome Measures

Primary Outcome Measures

Maximum Plasma Concentration (Cmax) [Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10,12 and 16, 24, 36 and 48 hours post dose]
Time for Cmax (Tmax) [Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10,12 and 16, 24, 36 and 48 hours]
Area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration (AUClast) [Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10,12 and 16, 24, 36 and 48 hours]
Area under the plasma concentration-time profile from time zero to 24 hours (AUC0-24) [Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10,12 and 16, 24, 36 and 48 hours]
Total amount of unchanged drug excreted in the urine over 24 hours, expressed as percent of dose (Ae24%) [Urine collection from 0 to 24 hours post dose]
Renal clearance (CLr) [Urine collection from 0 to 24 hours post dose]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Healthy male and/or female subjects of non-childbearing potential, between the ages of 18 and 55 years, inclusive (Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12 lead ECG and clinical laboratory tests).
Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight > 50 kg (110 lbs).
Japanese subjects must have four Japanese grandparents who were born in Japan.
Mean body weight and the body weight range of Western subjects must be within ±10% of the Japanese subjects.

Exclusion Criteria:

Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing).
Screening supine blood pressure >=140 mm Hg (systolic) or >=90 mm Hg (diastolic), on a single measurement (confirmed by a single repeat, if necessary) following at least 5 minutes of rest.
Any condition possibly affecting drug absorption (eg, gastrectomy).
History of regular alcohol consumption exceeding 7 drinks/week for females or 14 drinks/week for males (1 drink = 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of hard liquor) within 6 months of screening.
Treatment with an investigational drug within 30 days (or as determined by the local requirement, whichever is longer) or 5 half-lives preceding the first dose of study medication.
12-lead ECG demonstrating QTc >450 msec or a QRS interval >120 msec at screening. If QTc exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated two more times and the average of the three QTc or QRS values should be used to determine the subject's eligibility.
Pregnant or nursing females or women of childbearing potential.